4-Methylpyridine → 1-(3-Dibenzylamino-2,6-difluoro-phenyl)-2-pyridin-4-yl-ethanone

HRID 38104

Reaction equation

HRID 38104 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].C([O:25][C:26](=O)[C:27]1[C:32]([F:33])=[CH:31][CH:30]=[C:29]([N:34]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:28]=1[F:49])C1C=CC=CC=1.[Cl-].[NH4+]>O1CCCC1>[CH2:42]([N:34]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:29]1[C:28]([F:49])=[C:27]([C:26](=[O:25])[CH2:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)[C:32]([F:33])=[CH:31][CH:30]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 79634-Methylpyridine2×HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 584771183-Dibenzylamino-2,6-difluoro-benzoic acid benzyl ester

Product 1

HCID 584771201-(3-Dibenzylamino-2,6-difluoro-phenyl)-2-pyridin-4-yl-ethanoneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 4-methyl-pyridine (806 μL, 8.33 mmol) in anhydrous tetrahydrofuran (35 mL) was added at 0° C. sodium hexamethyldisilazide 1 M in tetrahydrofuran (16.66 mL, 16.66 mmol) and the reaction was stirred for 20 minutes. 3-Dibenzylamino-2,6-difluoro-benzoic acid benzyl ester (3.691 g, 8.33 mmol) was dissolved in tetrahydrofuran (5 mL) and added dropwise to the solution with 4-methyl-pyridine, the reaction was stirred at 0° C. for one hour. The reaction was poured into saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtrate and concentrated under reduced pressure. The crude was purified by silica gel column chromatography eluting with ethyl acetate 30% in hexane to give the title compound (1.775 g, 50%).

Workup

  1. stirringthe reaction was stirred at 0° C. for one hour
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate, filtrate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by silica gel column chromatography
  7. washeluting with ethyl acetate 30% in hexane

Sources & evidence

ORD record
ord-433b124ba76c40c0a4ec4512096d975c
Source dataset
uspto-grants-2013_09
Patent number
US08524707B2

Linked notes

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